LTBA NEWS

Category: Kentucky Equine Drug Research Council

The Kentucky Equine Drug Research Council (KEDRC) unanimously voted this week to allocate $15,000 to funding ongoing research into biological passport. Although the technology is at least a couple of years from implementation, Dr. Scott Stanley of the University of California-Davis said the passports could solve several problems in drug testing.

Regulators face particular challenges testing for long-acting prohibited substances like erythropoietin (EPO) and drugs creating steroid-like effects in the body. EPO in particular withdraws from the blood very quickly, but its impact (increasing the concentration of oxygen-carrying red blood cells in the body) lingers considerably longer. Both steroids and blood doping agents also tend to be used repeatedly but often weeks in advance of a race. Out-of-competition testing can act as a deterrent for these substances, but regulators still have a short window to actually find a positive level of the drugs in the horse’s system.

Biological passports track the responses of proteins and biomarkers to the administration of drugs like these even after the drugs themselves are gone. Stanley said the technology also gets around a common concern on the part of horsemen: what if a given horse, through no manipulation, is a natural outlier in the range of ‘normal’ for a hormone or protein? Sampling for passports would be taken repeatedly over an extended period of time, allowing regulators to compare a given reading not just with the normal range of the whole population, but also to the horse’s own previous readings.

Before the technology is ready for use at the racetrack though, Stanley and other researchers have to look at a range of markers in the equine body to decide which are the truest indicators of drug administration. Hormones and blood levels fluctuate naturally in response to the time of day, the season, and maybe a horse’s location.

Initial tests on a research horse looking at P27425 (an iron binding protein) produced exactly the results scientists expected. They plan to collect data from 50 to 100 horses in California in over one or more years to see how biomarkers behave in horses and which are the most consistent. When passport testing begins, Stanley anticipates a cross-section of horses will need to be sampled on a monthly basis in addition to post-race readings. As a greater cache of data is collected and stored, the monthly testing will become unnecessary.

The California Horse Racing Board and Grayson-Jockey Club Foundation have already provided funding to the project.

Dr. Andy Roberts, member of the KEDRC, questioned whether different (completely legal) training or feed routines could also cause a noticeable change in a horse’s passport levels. Stanley said it’s possible they could, so changes in passport readings would need to be taken as just a piece of the greater puzzle in what’s going on with a horse.

“Right now we would definitely see it as [a tool to initiate] an investigation: ‘This horse has been flagged for further follow-up’ and we’d get additional sequential samples from that to see if that horse is naturally outside the normal boundary,” said Stanley. “In the future, I think we could have enough additional data to say, ‘The upstream and downstream changes are not consistent with anything other than an administration.’ We just don’t have that data definitively yet to say what those changes should be.”

Unfortunately for equine researchers, the work that has been done on human biological passports with regard to blood-doping agents doesn’t seem as though it will be applicable to horses. The equine spleen is considerably different from that of humans, and its ability to suddenly contract with exertion causes changes in blood levels that would not be typical in a human.

The good thing about biological passports for racing regulators is that the technology won’t care what type of drug a trainer may have used to influence red blood cells or muscle tone, since they measure the body’s reaction instead of the size of drug molecules.

Like drug testing however, Stanley cautioned biological passports will be a constantly-evolving scientific process – but one that could have major impacts on integrity down the road.

“It isn’t a short-term project. It is years-long to get enough data,” he said. “The whole project is underfunded and it would take a long time even if it was fully-funded. I suspect we’ll be looking at more data in a couple years rather than a couple weeks.”

“The long-term intent is to provide deterrence. I truly believe that drug testing is about deterrence. We want to convince people we can test for everything and anything at any concentration that is prohibited. Just as we’re doing in Quarter Horse racing with a lot of hair testing right now, we would like to prevent [violators] from racing rather than penalize them after the race as an unfair competition.”

Like this:

Recommended withdrawal guidelines for detomidine, commercially known as Dormosedan, may face review after a recent study suggested horses could test positive while adhering to the guidelines. The current guideline from the Racing Medication Testing Consortium suggests the threshold for a positive be set at 2ng/ml in urine and 1 ngl/ml in blood, with the recommended withdrawal for a 5 mg intravenous dose set at 48 hours.

Detomidine is a relatively short-acting sedative with some analgesic properties and may be used to reduce stress during medical procedures or travel, or in hospital settings.

Recently, the Kentucky Equine Drug Research Council funded a study to examine the behavior of a 20 mg dose (given intravenously or intramuscularly), which some veterinarians say is also used in the field, depending upon the situation.

For tests of the drug using a blood sample, a 20 mg dose was well below the recommended threshold by 48 hours post-administration; in some cases the drug was almost undetectable. In the case of urine tests for detomidine however, several samples were over the threshold at 48 hours.

Unfortunately, the study was designed to stop at 48 hours post-administration, and therefore did not shed light on whether extending the window to 72 hours would be sufficient to avoid accidental positive tests.

“The dose that was investigated initially was a 5 mg dose. A lot of our veterinarians use a 5 mg dose. Dr. [Andy] Roberts and some other veterinarians wanted to know if they could use a 20 mg dose. It’s going to give a bigger effect,” he said. “Very few of these substances that affect the central nervous system have a dose that’s fixed. It’s a dose range, and I think it’s a legitimate question on Dr. Roberts’ part about using that 20 mg dose.”

Sams, who is a member of the RMTC’s Scientific Advisory Committee, said these types of revisions are to be expected as more information comes to light about different drugs and their behavior in horses. Unfortunately, there is a disparity between the public’s thirst for uniform regulations and the amount of time (and money) it takes to complete studies like this one, which ultimately highlights the need for more research.

“The process was moving very slowly years ago and the RMTC came under enormous pressure to move forward and have thresholds for all of these substances that veterinarians had identified. The future of the RMTC, I think, was on the line at that point,” Sams remembered. “We made some less-than-optimal choices with regard to doses, but veterinarians were involved in every step of the way.”